Observational Study

. 2025 May 26;25(1):221.

doi: 10.1186/s12883-025-04200-w.

Time to treatment in pediatric patients with repeated episodes of status epilepticus

Jennifer V Gettings¹, Iván Sánchez Fernández^{1

2}, Anne Anderson³, J Nicholas Brenton⁴, Afra Can⁵, Justice Clark¹, Raquel Farias Moeller⁶, Howard P Goodkin⁴, Yi-Chen Lai⁷, Mohamad A Mikati⁸, Lindsey A Morgan⁹, Edward Novotny^{9

10}, Adam P Ostendorf¹¹, Juan Piantino¹², James J Riviello³, Kumar Sannagowdara¹³, Robert C Tasker¹⁴, Dmitry Tchapyjnikov¹⁵, Mark S Wainwright⁹, Angus Wilfong¹⁶, Korwyn Williams¹⁶, Bo Zhang^{17

18}, Tobias Loddenkemper¹, Marina Gaínza-Lein^{19

20

21}; Pediatric Status Epilepticus Research Group (pSERG)

Affiliations

¹ Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
² Department of Child Neurology, Hospital Sant Joan de Déu, Universidad de Barcelona, Barcelona, Spain.
³ Division of Neurology and Developmental Neuroscience, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
⁴ Departments of Neurology and Pediatrics, University of Virginia, Charlottesville, VA, USA.
⁵ Division of Child Neurology, Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.
⁶ Department of Neurology, Division of Pediatric Neurology, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI, USA.
⁷ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
⁸ Division of Pediatric Neurology, Duke University Medical Center, Duke University, Durham, NC, USA.
⁹ Division of Child Neurology, Department of Neurology, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.
¹⁰ Norcliffe Foundation Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
¹¹ Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA.
¹² Division of Neurology, Doernbecher Children's Hospital, Oregon Health & Science University, Portland, OR, USA.
¹³ Child Neurology, Advocate Aurora Health Care, Epilepsy, Greenfield, WI, USA.
¹⁴ Division of Critical Care, Departments of Neurology, Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁵ Logan Health Children's Medical Center, Kallispell, MT, USA.
¹⁶ Department of Child Health, University of Arizona College of Medicine and Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA.
¹⁷ Department of Neurology, Boston Children's Hospital, Boston, Harvard Medical School, Boston, MA, USA.
¹⁸ Biostatistics and Research Design Center, Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁹ Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. m.gainzalein@gmail.com.
²⁰ Instituto de Pediatría, Facultad de Medicina, Universidad Austral de Chile, Independencia 631, Valdivia, Chile. m.gainzalein@gmail.com.
²¹ Facultad de Medicina, Universidad de Chile, Santiago, Chile. m.gainzalein@gmail.com.

PMID: 40420060
PMCID: PMC12105332
DOI: 10.1186/s12883-025-04200-w

Observational Study

Time to treatment in pediatric patients with repeated episodes of status epilepticus

Jennifer V Gettings et al. BMC Neurol. 2025.

. 2025 May 26;25(1):221.

doi: 10.1186/s12883-025-04200-w.

Authors

Affiliations

¹ Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
² Department of Child Neurology, Hospital Sant Joan de Déu, Universidad de Barcelona, Barcelona, Spain.
³ Division of Neurology and Developmental Neuroscience, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
⁴ Departments of Neurology and Pediatrics, University of Virginia, Charlottesville, VA, USA.
⁵ Division of Child Neurology, Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.
⁶ Department of Neurology, Division of Pediatric Neurology, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI, USA.
⁷ Division of Pediatric Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
⁸ Division of Pediatric Neurology, Duke University Medical Center, Duke University, Durham, NC, USA.
⁹ Division of Child Neurology, Department of Neurology, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.
¹⁰ Norcliffe Foundation Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
¹¹ Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA.
¹² Division of Neurology, Doernbecher Children's Hospital, Oregon Health & Science University, Portland, OR, USA.
¹³ Child Neurology, Advocate Aurora Health Care, Epilepsy, Greenfield, WI, USA.
¹⁴ Division of Critical Care, Departments of Neurology, Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁵ Logan Health Children's Medical Center, Kallispell, MT, USA.
¹⁶ Department of Child Health, University of Arizona College of Medicine and Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA.
¹⁷ Department of Neurology, Boston Children's Hospital, Boston, Harvard Medical School, Boston, MA, USA.
¹⁸ Biostatistics and Research Design Center, Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁹ Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. m.gainzalein@gmail.com.
²⁰ Instituto de Pediatría, Facultad de Medicina, Universidad Austral de Chile, Independencia 631, Valdivia, Chile. m.gainzalein@gmail.com.
²¹ Facultad de Medicina, Universidad de Chile, Santiago, Chile. m.gainzalein@gmail.com.

PMID: 40420060
PMCID: PMC12105332
DOI: 10.1186/s12883-025-04200-w

Abstract

Objective: To compare pediatric patients who presented with repeated status epilepticus episodes to patients with a single episode of status epilepticus and identify distinguishing clinical factors.

Methods: Retrospective analysis of a multicenter, prospective observational cohort of pediatric patients with status epilepticus between 2011 and 2019.

Results: Out of 504 status epilepticus episodes in 420 patients, 50 patients (10.3%) had repeated episodes of status epilepticus. The only predictor of repeated status epilepticus was a prior diagnosis of epilepsy. There was no difference in time to treatment with the first benzodiazepine in patients presenting with their first status epilepticus episode compared to their second status epilepticus episode [median 10 (interquartile range 5-30) vs. 14 (4.5-52.5) minutes; (p = 0.24)] or in time to treatment with the first non- benzodiazepine anti-seizure medication (ASM) [61 (37-125) vs. 71 (34.5-117.5) minutes; p = 0.61]. In patients with repeated status epilepticus episodes with onset outside the hospital, the percentage of patients treated by caregivers did not improve between the first and second status epilepticus episode (61% vs. 60%, p = 0.56). However, the time to first benzodiazepine was shorter in patients treated by caregivers compared to those who were not [5 (0-25) vs. 55 (41-120) minutes; p < 0.001].

Conclusions: Time to treatment with benzodiazepine and non-benzodiazepine ASM in patients with repeated episodes of status epilepticus does not improve for a second episode of status epilepticus, suggesting additional opportunities for intervention and teaching.

Keywords: Anti-seizure medications; Benzodiazepines; Refractory status epilepticus; Status epilepticus; Treatment delay.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: The research protocol was approved by the institutional review boards of all participating institutions, including Boston Children’s Hospital (IRB P-00001207), and written informed consent was obtained from all participants, parents, or guardians. Consent for publication: Not applicable. Competing interests: Dr. Jennifer Gettings receives research support from NIH. Dr. J. Nicholas Brenton receives research support from NIH. He has served as a consultant for Cycle Pharmaceuticals and the Institute for Advanced Clinical Trials (I-ACT) for Children on a Novartis-sponsored project. Dr. Adam Ostendorf receives research support from NIH Dr. Edward Novotny was on the Advisory Board for Longboard Pharmaceuticals, Inc. Dr. Mark Wainwright is a member of the Clinical Advisory Board for Sage Therapeutics. Dr. Tobias Loddenkemper receives research support from NIH, Epitel, Sumitomo, and the Epilepsy Research Fund. He received past research support from Upsher Smith, Proximagen, MIKU, and UCB. Dr. Tobias Loddenkemper is part of patent applications to detect and predict clinical outcomes, and to detect, manage, diagnose, and treat neurological conditions, epilepsy, and seizures. Some of Dr. Tobias Loddenkemper’s trainees received salary support from international foundations/societies and academic centers while working in his laboratory. Dr. Marina Gaínza-Lein was previously funded by the Epilepsy Research Fund.

Figures

**Fig. 1**
Inclusion and exclusion criteria

**Fig. 2**
Time to treatment with first BZD in the first (group IIa) compared to the second (group IIb) status epilepticus (SE) episode. The time to treatment [median (IQR)] with the first BZD was not different in patients in the first compared to the second SE episode [10 (5–30) minutes vs. 14.5 (4.5–52.5); (p = 0.24)]. Circles represent outliers greater than 3rd quartile plus 1.5 times interquartile range or less than 1st quartile minus 1.5 times interquartile range; asterisks represent extreme outliers greater than 3rd quartile plus 3 times interquartile range or less than 1st quartile minus 3 times interquartile range; an extreme outlier with a value of 1605 min which occurred during the second episode is not displayed

**Fig. 3**
Time to treatment with first non-benzodiazepine (BZD) in the first (group IIa) compared to the second (group IIb) status epilepticus (SE) episode. The time to treatment [median (IQR)] with the first non-BZD anti-seizure medication (ASM) was not different in patients in the first compared to the second SE episode [61 (37–125) minutes vs. 71 (34.5-117.5) minutes; p = 0.61]. Circles represent outliers greater than 3rd quartile plus 1.5 times interquartile range or less than 1st quartile minus 1.5 times interquartile range; asterisks represent extreme outliers greater than 3rd quartile plus 3 times interquartile range or less than 1st quartile minus 3 times interquartile range; an extreme outlier with a value of 1031 min which occurred during the second episode is not displayed

**Fig. 4**
Time to treatment with first benzodiazepine (BZD) in patients with repeated status epilepticus (SE) episodes (group II) with onset in the pre-hospital setting. Time to treatment [median (IQR)] with the first BZD was significantly shorter in patients treated by family members than in patients not treated by family members [5 (0–25) minutes vs. 55 (41–120) minutes, (p < 0.001)]. Circles represent outliers greater than 3rd quartile plus 1.5 times interquartile range or less than 1st quartile minus 1.5 times interquartile range; asterisks represent extreme outliers greater than 3rd quartile plus 3 times interquartile range or less than 1st quartile minus 3 times interquartile range; an extreme outlier with a value of 1605 min which occurred during the second episode and was treated by family is not displayed

See this image and copyright information in PMC

References

1. Chin RF, Neville BG, Peckham C, Bedford H, Wade A, Scott RC. Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study. Lancet. 2006;368(9531):222–9. - PubMed
1. Chin RF, Neville BG, Scott RC. A systematic review of the epidemiology of status epilepticus. Eur J Neurol. 2004;11(12):800–10. - PubMed
1. Neligan A, Noyce AJ, Gosavi TD, Shorvon SD, Köhler S, Walker MC. Change in mortality of generalized convulsive status epilepticus in High-Income countries over time: A systematic review and Meta-analysis. JAMA Neurol. 2019;76(8):897–905. - PMC - PubMed
1. Martinos MM, Yoong M, Patil S, Chong WK, Mardari R, Chin RF, et al. Early developmental outcomes in children following convulsive status epilepticus: a longitudinal study. Epilepsia. 2013;54(6):1012–9. - PubMed
1. Raspall-Chaure M, Chin RF, Neville BG, Scott RC. Outcome of paediatric convulsive status epilepticus: a systematic review. Lancet Neurol. 2006;5(9):769–79. - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions

LinkOut - more resources

Full Text Sources
- BioMed Central
- PubMed Central

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Time to treatment in pediatric patients with repeated episodes of status epilepticus

Affiliations

Time to treatment in pediatric patients with repeated episodes of status epilepticus

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources